RT Journal Article
SR Electronic
T1 Novel Lipid Mediator Regulators of Endothelial Cell Proliferation and Migration: Aspirin-Triggered-15<em>R</em>-Lipoxin A<sub>4</sub> and Lipoxin A<sub>4</sub>
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 385
OP 392
DO 10.1124/jpet.300.2.385
VO 300
IS 2
A1 Iolanda M. Fierro
A1 Jeffery L. Kutok
A1 Charles N. Serhan
YR 2002
UL http://jpet.aspetjournals.org/content/300/2/385.abstract
AB Proliferative states such as chronic inflammation, ischemic diseases, and cancer are often accompanied by intense angiogenesis, a highly orchestrated process involving vessel sprouting, endothelial cell migration, proliferation, and maturation. Aspirin-triggered lipoxins (ATLs), the 15R enantiomeric counterparts of lipoxins (LXs), are endogenous mediators generated during multicellular responses that display potent immunomodulatory actions. Herein, we report a novel action for the ATL stable analog 15-epi-16-(para-fluoro)-phenoxy-lipoxin A4(denoted ATL-1), which proved to be a potent inhibitor of angiogenesis. This ATL inhibited endothelial cell proliferation in the 1 to 10 nM range by ∼50% in cells stimulated with either vascular endothelial growth factor (VEGF) at 3 ng/ml or leukotriene D4 at 10 nM. In addition, ATL-1 (in a 10–100 nM range) inhibited VEGF (3 ng/ml)-induced endothelial cell chemotaxis. In a granuloma in vivo model of inflammatory angiogenesis, ATL-1 treatment (10 μg/mouse) reduced by ∼50% the angiogenic phenotype, as assessed by both vascular casting and fluorescence. Together, these results identify a novel and potent previously unappreciated action of aspirin-triggered 15-epi-LX. The American Society for Pharmacology and Experimental Therapeutics